The role of cyclic nucleotides in neutrophil migration

1. The literature concerning the effects of cAMP and especially cGMP on neutrophil migration is reviewed. 2. Experiments with agents that enhance cGMP level, and with electroporated neutrophils in which cGMP was introduced, show that the nucleotide has different effects. There is a maximal stimulation at a specific concentration while higher concentrations are less effective or even inhibitory. 3. Some physiologically active peptides such as granulocyte-macrophage colony-stimulating factor (GM-CSF), atrial natriuretic factor, and endothelin appear to modify neutrophil migration via a cGMP-dependent mechanism. 4. Dependent on concentration and conditions (random migration vs. fMLP-activated migration, using nitric oxide (NO), NO donors, and inhibitors of NO synthase), NO has stimulatory or inhibitory effects on neutrophil migration. 5. The differential effects of cGMP and cAMP on neutrophil migration are discussed with regard to intracellular actions, metabolism, interaction with calcium, and relation to structural changes required for cell movement.